Patient-oriented biomedical investigation related to diagnosis, disease mechanisms, monitoring disease activity and new therapeutic approaches in rheumatic disease is the hallmark of the Johns Hopkins Division of Rheumatology. This research is structured around well-established disease-specific Centers of Excellence in scleroderma (Dr. Fred Wigley), lupus (Dr. Michelle Petri), arthritis (Dr. Joan Bathon), and vasculitis (Dr. John Stone). These clinical cohorts are coupled closely with a robust basic science program directed by Drs. Antony Rosen and Livia Casciola-Rosen. In recent years, this program has received outstanding institutional support, enabling significant growth, investment in shared equipment and infrastructure, and the initiation of multiple synergistic projects both within and outside the Division. Our Rheumatic Disease Research Core Center (RDRCC) proposal capitalizes upon the strong biomedical research base within the Division of Rheumatology, as well as additional outstanding talent from the broader scientific community at Johns Hopkins. The Hopkins RDRCC proposal comprises an Administrative Core (Core A) led by Drs. Antony Rosen and John Stone, and includes 2 Scientific Cores: 1) a Bioassay Core (Core B), led by Drs. James Mahoney, Mark Soloski, and Livia Casciola-Rosen; and 2) a Genotyping/Genomics Core (Core C), led by Dr. Kathleen Barnes, designed to foster new research within and beyond the Division's Disease Centers. Core A will promote interdisciplinary research through the cores, provide assistance with financial management, provide information technology solutions to maximize efficiency of translational research, and coordinate program enrichment activities. The Administrative core will also manage the Pilot and Feasibility program. Pilot studies chosen for the first year are tightly linked to the disease Centers and Cores. Pilot #1 will optimize assays to quantify clearance of apoptotic cells directly ex vivo in pediatric SLE patients. Pilot #2 will explore the association of genetic polymorphisms in granzyme B with specific phenotypes in scleroderma. Core B will provide assistance with patient sample acquisition, processing, storage, and distribution, as well as the provision of multiple immunological assays, including FACS, ELISA, immunohistology, and multiplex cytokine assays. Core C will perform, analyze, and interpret gene expression studies in a variety of human disease and control tissues and some mouse models. Core C will also oversee the design, performance and analysis of genetic association studies in well-defined human rheumatic phenotypes.